20-10641432-CAA-CAAA

Variant names:

• chr20-10641432-C-CA
• rs3215563
• NM_000214.3:c.2916+27dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000214.3(JAG1):​c.2916+27dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1537 hom., cov: 0)
  • Exomes 𝑓: 0.15 (5575 hom.)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.173
• Publications: 3 publications found

Genes affected

JAG1 (HGNC:6188): (jagged canonical Notch ligand 1) The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]

JAG1 Gene-Disease associations (from GenCC):

• Alagille syndrome due to a JAG1 point mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• Charcot-Marie-Tooth disease, axonal, Type 2HH

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-10641432-C-CA is Benign according to our data. Variant chr20-10641432-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1260067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAG1	NM_000214.3	MANE Select	c.2916+27dupT		intron	N/A	NP_000205.1	P78504-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAG1	ENST00000254958.10	TSL:1 MANE Select	c.2916+27_2916+28insT		intron	N/A	ENSP00000254958.4	P78504-1
	JAG1	ENST00000901230.1		c.2916+27_2916+28insT		intron	N/A	ENSP00000571289.1
	JAG1	ENST00000913738.1		c.2910+27_2910+28insT		intron	N/A	ENSP00000583797.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 20713 AN: 149082 Hom.: 1536 Cov.: 0

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00197

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.151 AC: 200270 AN: 1329438 Hom.: 5575 Cov.: 13 AF XY: 0.149 AC XY: 99144 AN XY: 663966

African (AFR) AF: 0.146 AC: 4251 AN: 29084

American (AMR) AF: 0.132 AC: 5661 AN: 42836

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3028 AN: 24268

East Asian (EAS) AF: 0.00179 AC: 63 AN: 35222

South Asian (SAS) AF: 0.115 AC: 9233 AN: 80260

European-Finnish (FIN) AF: 0.115 AC: 5536 AN: 48128

Middle Eastern (MID) AF: 0.107 AC: 568 AN: 5286

European-Non Finnish (NFE) AF: 0.163 AC: 164479 AN: 1009264

Other (OTH) AF: 0.135 AC: 7451 AN: 55090

GnomAD4 genome AF: 0.139 AC: 20725 AN: 149182 Hom.: 1537 Cov.: 0 AF XY: 0.134 AC XY: 9740 AN XY: 72758

African (AFR) AF: 0.139 AC: 5606 AN: 40324

American (AMR) AF: 0.114 AC: 1713 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 421 AN: 3454

East Asian (EAS) AF: 0.00197 AC: 10 AN: 5064

South Asian (SAS) AF: 0.111 AC: 524 AN: 4706

European-Finnish (FIN) AF: 0.110 AC: 1100 AN: 9968

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 10961 AN: 67340

Other (OTH) AF: 0.121 AC: 250 AN: 2072

Alfa AF: 0.123 Hom.: 552

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3215563; hg19: chr20-10622080;